Detection of 13q deletion in patients with chronic lymphocytic leukemia and its correlation to hematopathological parameters
Keywords:
detection, 13q deletion, patients, lymphocytic leukemia, hematopathological parametersAbstract
Background: Chronic lymphocytic leukemia(CLL) is a monoclonal malignancy characterized by an accumulation of small and mature looking B lymphocytes in the blood, bone marrow and other tissues, and is typically characterized by expression CD5+, CD23+, CD22 -, CD79b-, with weak expression of surface immunoglobulin (sIg). Two major clinical staging systems (Rai and Binet staging), that developed to estimate prognosis in CLL. However both these systems are unable to prospectively distinguish the rapidly developing patients from those appreciated to remain with a stable disease for decades. Several publications reported the prognostic important of 13q deletion in patients with chronic lymphocytic leukemia. 13q deletion is the most important cytogenetic abnormalities detected by Fluorescence In situ Hybridization in CLL patients and represent a good prognostic marker with 60% of patients alive after 5 years as compared with 27% for patients with a normal FISH analysis. Aims of the study: To investigate 13q deletion in patients with chronic lymphocytic leukemia by using FISH technique. To correlate the presence of 13q deletion with hematological and clinical prognostic markers including complete blood picture, absolute lymphocyte count, and modified Rai staging.
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102 Basabaeen AA, Abdelgader EA, Babekir EA, et al. Clinical presentation and hematological profile among young and old chronic lymphocytic leukemia patients in Sudan. BMC Res Notes. 2019;12(1):202.
32 Ravindran A, Kyle R, Sankaran J, Jacob E, Kreuter J, Hook CC, Gertz M, Call T, Marshall A, Pruthi R, Ashrani A. High prevalence of monoclonal gammopathy among patients with warm autoimmune hemolytic anemia. American Journal of Clinical Pathology. 2016 Sep 1;146(suppl_1).
35 Ten Hacken E, Burger JA. Microenvironment interactions and B-cell receptor signaling in chronic lymphocytic leukemia: implications for disease pathogenesis and treatment. BiochimicaetBiophysicaActa (BBA)-Molecular Cell Research. 2016 Mar 31; 1863(3):401-13.
A. E. Rodriguez, J. A. Hernandez, R. Benito et al., Molecular characterization of chronic lymphocytic leukemia patients with a high number of losses in 13q14, PLoS ONE, vol.7 , no. 11, 2012.
A. Puiggros, J. Delgado, A. Rodriguez-Vicente et al., Biallelic losses of 13q do not confer a poorer outcome in chronic lymphocytic leukemia: analysis of 627 patients with isolated 13q deletion, The British Journal of Hematology, vol. 163, no. 1, pp. 47-54, 2013.
Abbott BL. Chronic lymphocytic leukemia: Recent advances in diagnosis and treatment. Oncologist. 2006;11:21–30. doi: 10.1634/theoncologist.11-1-21.
Abrisqueta P, Pereira A, Rozman C, Aymerich M, Gine E, Moreno C, et al. Improving survival in patients with chronic lymphocytic leukemia (1980–2008): the Hospital Clinic of Barcelona experience. Blood. 2009;114(10):2044–50
Acunzo M, Croce CM. Downregulation of miR-15a and miR-16-1 at 13q14 in Chronic Lymphocytic Leukemia. Clinical chemistry.2016 Apr 1; 62(4):655-6.
Agarwal MB, Bhurani D, Shah C, et al. Efficacy and Safety of Ibrutinib in Indian Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma: Cases from a Named Patient Program. Indian J Med Paediatr Oncol. 2017;38(4):508–515.
Agrawal N, Naithani R, Mahapatra M, Panigrahi I, Kumar R, Pati HP, Saxena R, Choudhary VP. Chronic lymphocytic leukemia in India—a clinico-hematological profile. Hematology (Amsterdam, Netherlands) 2007;12(3):229–233
Arumugakani G, Thompson J, Khukhar F, de Tute RM, Tooze R, Emery P, McGonagle D, Rawstron AC. THU0002 Prevalence of Monoclonal B-Cell Disorders in Patients with Autoimmunity in The UK.
Baliakas P, Kanellis G, Stavroyianni N, Fameli M, Anagnostopoulos A, Stamatopoulos K, Papadaki T. The role of bone marrow biopsy examination at diagnosis of chronic lymphocytic leukemia.Leukemia & lymphoma. 2013 Nov 1; 54(11):2377-84.
Baliakas P, Puiggros A, Xochelli A, Sutton LA, Nguyen-Khac F, Gardiner A, Plevova K, Minga E, Hadzidimitriou A, Walewska R, McCarthy H. Additional trisomies amongst patients with chronic lymphocytic leukemia carrying trisomy 12: the accompanying chromosome makes a difference. haematologica. 2016 Jul 1; 101(7):e299-302.
BCSH Secretary. Guidelines on the diagnosis and management of chronic lymphocytic leukaemia. British Journal of Haematology2004; 125: 294–317
Brenner H, Gondos A, Pulte D. Trends in long-term survival of patients with chronic lymphocytic leukemia from the 1980s to the early 21st century. Blood. 2008;111(10):4916–21
Brown JR, MD, PhD. Inherited predisposition to chronic lymphocytic leukemia, Expert Review of Hematology. October 2008; Vol.1, No.1: Pages: 51-61.
Bullrich F. & Croce, C. M. (2001) in Chronic Lymphoid Leukemias, ed. Chenson, B. D. (Dekker, New York), pp. 9–32.
Burger JA, Gribben JG. The microenvironment in chronic lymphocytic leukemia (CLL) and other B cell malignancies: disease biology and new targeted therapies. Cancer Biology 2014 (No. 24, p.71-81).
Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99(24):15524–15529.
Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 2005; 353: 1793–1801.
Call TG, Nomman AD, Hason CA. Incidince of chronic lymphocytic leukemia and high count MBL using the 2008 Guidelines.Cancer.2014; 120(13).
Call TG, Phyliky RL, Noel P, Habermann TM, Beard CM, O’Fallon WM, et al. Incidence of chronic lymphocytic leukemia in Olmsted County, Minnesota, 1935 through 1989, with emphasis on changes in initial stage at diagnosis. Mayo Clinic Proceedings Mayo Clinic. 1994;69(4):323–8
Cappelletti F, Clementi N, Mancini N, Clementi M, Burioni R. Virus-induced preferential antibody gene-usage and its importance in humoral autoimmunity. InSeminars in immunology 2015 Mar 31 (Vol. 27, No. 2, pp. 138-143).Academic Press.
Catovsky D, Müller-Hermelink HK, Ralfkiaer E. T-cell prolymphocytic leukemia. WHO classification of tumours of haematopoietic and lymphoid tissues 2008.
Chang CC, Liu CZ, Cleveland R. Prognostic implications of CD38 markers expression in B-CLL. Blood. 2000 Nov 16(96), No. 11,p:372-372.
D. L. van Dyke , T. D. Shanafelt, T. G. Call et al., A comprehensive evaluation of the prognostic significance of 13q deletions in patients with chronic lymphocytic leukemia, The British Journal of Hematology, vol. 148, no.4, pp. 544-550, 2010.
D. Mertens, S. Wolf, C. Tschuch et al., Allelic silencing at the tumor-suppressor locus 13q14.3 suggests an epigenetic tumor-suppressor mechanism, Proceedings of the National Academy of Sciences of the United States Of America, vol. 103, no. 20, pp. 7741-7746, 2006.
Dal Bo M, Rossi FM, Rossi D, Deambrogi C, Bertoni F, Del Giudice I, et al. 13q14 deletion size and number of deleted cells both influence prognosis in chronic lymphocytic leukemia. Genes Chromosomes Cancer. 2011;50:633–643.
Dohner H., Stilgenbauer, S., Benner, A., Leupolt, E., Krober, A., Bullinger, L., Dohner, K., Bentz, M. & Lichter, P. (2000) N. Engl. J. Med. 343 1910-1916.
Dolcetti R, Carbone A. Epstein-Barr virus infection and chronic lymphocytic leukemia: a possible progression factor. Infectious agents and cancer. 2010 Nov 22;5(1):22.
Doni E, Carli G, Di Rocco A, Sassone M, Gandolfi S, Patti C, Falisi E, Salemi C, Visco C. Autoimmune haemolyticanaemia in mantle cell lymphoma: an insidious complication associated with leukemic disease. Hematological oncology. 2017 Mar 1;35(1):135-7.
E. M. Orlandi, P .Bernasconi, C. Pascutto et al ., Chronic lymphocytic leukemia with deletion 13q14 as the sole abnormality: dynamic prognostic estimate by interphase-FISH, Hematological Oncology, vol. 31, no. 3, pp. 136-142, 2013.
Fabbri M, Bottoni A, Shimizu M, Spizzo R, Nicoloso MS, Rossi S, Barbarotto E, Cimmino A, Adair B, Wojcik SE, Valeri N. Association of a microRNA feedback circuitry with pathogenesis and outcome of B-cell chronic lymphocytic leukemia. Jama. 2011 Jan 5; 305(1):59-67.
Ferrajoli A. Treatment of younger patients with chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2010;82–9
G.A. Calin, C. D. Dumitru,M. Shimizu et al., frequent deletions and downregulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia, proceedings of the national academy of sciences of the united states of America, vol.99, no.24,pp. 15524-15529, 2002.
García-Muñoz, Ricardo, VerónicaRoldanGaliacho, and Luis Llorente. “Immunological Aspects in Chronic Lymphocytic Leukemia (CLL) Development.” Annals of Hematology 91.7 (2012): 981–996.
George TI. Malignant or benign leukocytosis. Hematology Am SocHematol Education Program. 2012:475-484.
Goldin LR, Pfeiffer RM, Li X, Hemminki K. Familial risk of lymphoproliferative tumors in families of patients with chronic lymphocytic leukemia. Blood. 2004 Sep 15; 104 (6):1850-4.
Gribben J. (2010) How I treat CLL up front. Blood 115: 187–197.
Gribben JG. Chronic lymphocytic leukemia: planning for an aging population. Expert Rev Anticancer Ther. 2010;10(9):1389–1394.
Grygalewicz B, Woroniecka R, Rygier J, Borkowska K, Rzepecka I, Łukasik M, Budziłowska A, Rymkiewicz G, Błachnio K, Nowakowska B, Bartnik M. Monoallelic and biallelic deletions of 13q14 in a group of CLL patients investigated by CGH Haematological Cancer and SNP array .Molecular cytogenetics. 2016 Jan 6; 9(1):1.
Gulati G, Ly V, Uppal G, Gong J. Can the Smudge Cells Be Counted As Lymphocytes in the Differential Leukocyte Counts Performed on Peripheral Blood Smears of Chronic Lymphocytic Leukemia Patients?.American Journal of Clinical Pathology. 2016 Sep 1;146(suppl_1):160.
H. Parker, M. J.J. Rose-zerilli, A. Parker et al., 13q deletion anatomy and disease progression in patients with chronic lymphocytic leukemia, leukemia, vol.25, no. 3, pp. 489-497, 2011.
Hallek M, Cheson BD, Catovsky D. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the InternationalWorkshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute–Working Group 1996 guidelines. Blood 2008; 111(12): 5446- 5456.
Hallek M, Kuhn-Hallek I, Emmerich B. Prognostic factors in chronic lymphocytic leukemia. Leukemia. 1997: 11 (2): S4-13
Hallek M. Chronic lymphocytic leukemia: 2017 update on diagnosis, risk stratification, and treatment. American journal of hematology. 2017 Sep 1;92(9):946-65.
Hanlon K, Rudin CE, Harries LW. Investigating the targets of MIR-15a and MIR-16-1 in patients with chronic lymphocytic leukemia (CLL). PLoS One. 2009;4(9):e7169.
Hasan KM. Clinical Aspects, Immunophenotypic Analysis and Survival Rate of Chronic Lymphocytic Leukaemia Patients in Erbil City, Iraq. Sultan Qaboos Univ Med J. 2018;18(4):e461–e467.
Heng HHQ, Squire J, Tsui L-C. High resolution mapping of mammalian genes by in situ hybridization to free chromatin .ProcNatlAcadSci USA 1992; 89: 9509–9513.
Henriques A., Rodríguez-Caballero A., Criado I., Langerak A.W., Nieto W. “Molecular and Cytogenetic Characterization of Expanded B-Cell Clones from Multiclonal versus Monoclonal B-Cell Chronic Lymphoproliferative Disorders.” Haematologica 99.5 (2014): 897–907. (Doctoral dissertation).
Herndon TM, Chen SS, Saba NS, Valdez J, Emson C, Gatmaitan M, Tian X, Hughes TE, Sun C, Arthur DC, Stetler-Stevenson M. Direct in vivo evidence for increased proliferation of CLL cells in lymph nodes compared to bone marrow and peripheral blood. Leukemia. 2017 Jun; 31(6):1340.
His B-L, Xiao S, Fletcher JA. Chromogenic in situ hybridization and FISH in Pathology . In: Fan Y-S (ed.) Methods in Molecular Biology, Vol 204: Molecular Cytogenetics: Protocols and Applications. Totowa, NJ : Humana Press Inc. ; 2002; 343–351. 13 Wolff DJ, Bagg A, Cooley LD et al. Guidance for fluorescence in situ hybridization testing in hematologic disorders . J MolDiagn 2007; 9: 134–1
Hung PJ, Chen BR, George R, Liberman C, Morales AJ, Colon-Ortiz P, Tyler JK, Sleckman BP, Bredemeyer AL. Deficiency of XLF and PAXX prevents DNA double-strand break repair by non-homologous end joining in lymphocytes. Cell Cycle. 2017 Feb 1; 16(3):286-95.
J. A. Hernandez, A. E. Rodriguez, M. Gonzalez et al., A high number of losses in 13q14 chromosome band is associated with a worse outcome and biological differences in patients with B-cell chronic lymphoid leukemia, Haematologica, vol. 94, no. 3, pp. 364-371, 2009.
Jenkins RB, LeBeau MM, Kraker WJ et al. Fluorescence in situ hybridization: A sensitive method for trisomy 8 detection in bone marrow specimens .Blood 1992; 79: 3307–3315.
Jiang Y, Chen HC, Su X, Thompson PA, Liu X, Do KA, Wierda W, Keating MJ, Plunkett W. ATM function and its relationship with ATM gene mutations in chronic lymphocytic leukemia with the recurrent deletion (11q22. 3-23.2). Blood cancer journal. 2016 Sep; 6(9):e465.
Juliusson G., Oscier, D. G., Fitchett, M., Ross, F. M., Stockdill, G., Mackie, M. J., Parker, A. C., Castoldi, G. L., Guneo, A., Knuutila, S., et al. (1990) N. Engl. J. Med. 323 720-724.
K. S. Reddy, Chronic lymphocytic leukemia profiled for prognosis using fluorescence insitu hybridization panel, The British Journal of Hematology, vol. 132, no. 6, pp. 705-722, 2006.
Khoudoleeva O, Gretsov E, Barteneva N, Vorobjev I. Proliferative index and expression of CD38, Zap-70 in different lymphoid compartments of chronic lymphocytic leukemia patients. Pathol Lab Med Int. 2011; 3:7-16.
Kiefer Y, Schulte C, Tiemann M, Bullerdiek J. Chronic lymphocytic leukemia-associated chromosomal abnormalities and miRNA deregulation. Appl Clin Genet. 2012;5:21–28.
Kolibaba KS, Sterchele JA, Joshi AD, et al. Demographics, treatment patterns, safety, and real-world effectiveness in patients aged 70 years and over with chronic lymphocytic leukemia receiving bendamustine with or without rituximab: a retrospective study. Ther Adv Hematol. 2013;4(3):157–171.
Korde N, Zhang Y, Loeliger K, Poon A, Simakova O, Zingone A, Costello R, Childs R, Noel P, Silver S, Kwok M. Monoclonal gammopathy‐associated pure red cell aplasia. British journal of haematology. 2016 Jun 1;173(6):876-83.
L. Mosca, S. Fabris, M. Lionetti et al., Integrative genomics analyses reveal molecularly distinct subgroups of B-cell chronic lymphocytic leukemia patients with 13q14 deletion, clinical cancer research, vol 16, no.23, pp. 5641-5653, 2010.
Lai YY, Huang XJ. Cytogenetic characteristics of B cell chronic lymphocytic leukemia in 275 Chinese patients by fluorescence in situ hybridization: a multicenter study. Chin Med J. 2011;124(16):2417–22.
Lazarian G, Tausch E, Eclache V, Sebaa A, Bianchi V, Letestu R, Collon JF, Lefebvre V, Gardano L, Varin‐Blank N, Soussi T. TP53 mutations are early events in chronic lymphocytic leukemia disease progression and precede evolution to complex karyotypes. International journal of cancer. 2016 Oct 15;139(8):1759-63.
Lee YE, Hong CY, Lin YL, Chen RM. MicroRNA-1 participates in nitric oxide-induced apoptotic insults to MC3T3-E1 cells by targeting heat-shock protein-70. International journal of biological sciences. 2015;11(3):246.
Lynch HT, Weisenburger DD, Quinn‐Laquer B, Watson P, Lynch JF, Sanger WG. Hereditary chronic lymphocytic leukemia: an extended family study and literature review. American Journal of Medical Genetics Part A.2002 Oct 30; 115(3):113-7.
M. Dal Bo, F. M. Rossi, D. Rossi et al., 13q14 deletion size and number of deleted cells both influence prognosis in chronic lymphocytic leukemia, Genes, Chromosomes and Cancer, vol. 50, no. 8, pp. 633-643, 2011.
Mamidi S, Höne S, Kirschfink M. The complement system in cancer: Ambivalence between tumour destruction and promotion. Immunobiology. 2017 Jan 31;222(1):45-54.
Marti GE, Shim YK, Albitar M, Middleton D, Abbasi F, Anderson A, Vogt RF. Long‐term follow‐up of monoclonal B‐cell lymphocytosis detected in environmental health studies. Cytometry Part B: Clinical Cytometry. 2010 Jan 1; 78.
Matutes E, Morilla R, et al. Immunophenotyping. In: Bain BJ, Lewis SM. Dacie and Lewis Practical Haematology 11th edition. Churchill Livingstone Elsevier; 2011:p368.
Matutes E, Polliack A. Morphological of chronic lymphocytic leukemia, Hematol. 2000 Mar; 4(1):22-47.
Metasystems Probes. Available at https://metasystems-probes.com/en/probes/xl/d-5054-100-og/; Accessed on April the 6th 2019
Micale MA, Sanford JS, Powell IJ et al. Defining the extent and nature of cytogenetic events in prostatic adenocarcinoma: paraffi n FISH vs. metaphase analysis .Cancer Genet Cytogenet 1993; 69: 7–12.
Ministry of Health, Results on Iraqi Cancer Registry 2010, Iraqi Cancer Board, Baghdad-Iraq.
Montillo M, O'Brien S, Tedeschi A, et al. Ibrutinib in previously treated chronic lymphocytic leukemia patients with autoimmune cytopenias in the RESONATE study. Blood Cancer J. 2017;7(2):e524.
Moreau EJ, Matutes E, A’hern RP, Morilla AM, Morilla RM, Owusu-Ankomah KA, Seon BK, Catovsky D. Improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody CD79b. American journal of clinical pathology. 1997 Oct 1; 108(4):378-82.
National Center for Biotechnology Information USNLoM.CD38 molecule. Available at: http://www.ncbi.nlm.nih.gov (Accessed at May 24, 2016).
Ning Y, Roschke A, Smith ACM et al. A complete set of human telomeric probes and their clinical application . Nat Genet 1996; 14: 86–89.82. Popp S, Jauch A, Schindler D et al. A strategy for the characterization of minute chromosome rearrangements using multiple color fluorescence in situ hybridization with chromosome - specifi c DNA libraries and YAC probes . Hum Genet 1993; 92: 527–532.
Oscier D. G., Gardiner, A. C., Mould, S. J., Glide, S., Davis, Z. A., Ibbotson, R. E., Corcoran, M. M., Chapman, R. M., Thomas, P. W., Copplestone, J. A., et al. (2002) Blood 100 1177-1184.
Ouillette P, Collins R, Shakhan S, et al. The prognostic significance of various 13q14 deletions in chronic lymphocytic leukemia. Clin Cancer Res. 2011;17(21):6778–6790.
P. Ouillette, H. Erba, L. Kujawski, M. Kaminski, K. Shedden, and S. N. Malek, Integrated genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion13q14, Cancer Research, vol. 68, no.4, pp. 1012-1021, 2008.
Parikh SA, Rabe KG, Kay NE, et al. Chronic lymphocytic leukemia in young (≤ 55 years) patients: a comprehensive analysis of prognostic factors and outcomes. Haematologica. 2014;99(1):140–147.
Pavlović S, Stojiljković M, Tošić N, Zukić B, Ugrin M, Karan-Djurašević T, Spasovski V. Genomics as a basis for precision medicine. BiologiaSerbica. 2017 Jul 20; 39(1).
Podhorecka M, Halicka D, Szymczyk A, Macheta A, Chocholska S, Hus M, Darzynkiewicz Z. Assessment of red blood cell distribution width as a prognostic marker in chronic lymphocytic leukemia. Oncotarget. 2016 May 31; 7(22):32846.
R. Garg, W. Wierda, A. Ferrajoli et al., The prognostic difference of monoallelic versus biallelic deletion of 13q in chronic lymphocytic leukemia, Cancer, vol. 118, no. 14,pp. 3531-3537 ,2012.
Rai KR, Keating MJ, Kufe DW, Pollock RE, Weichselbaum RR. Clinical Staging and Other Prognostic Features. Holland-Frei Cancer Medicine.6th edition.Hamilton BC Decker; 2003. Available from: https://www.ncbi.nlm.nih.gov/books/NBK12992/
Rai KR. 1 Progress in chronic lymphocytic leukaemia: A historical perspective. Baillière's clinical haematology.1993 Dec 1; 6(4):757-65.
Redaelli A, Laskin BL, Stephens JM, Botteman MF, Pashos CL. The clinical and epidemiological burden of chronic lymphocytic leukaemia.European journal of cancer care. 2004 Jul 1; 13(3):279-87.
Redaelli, A, Laskin BL, Stephens JM, Botteman MF, and Pashos CL. The clinical and epidemiological burden of chronic lymphocytic leukemia.Eur J Cancer Care 2004; Jul; 13(3):279-87.
Rodrigues CA, Gonçalves MV, Ikoma MR, et al. Diagnosis and treatment of chronic lymphocytic leukemia: recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia [published correction appears in Rev Bras Hematol Hemoter. 2017 Jan - Mar;39(1):93-94]. Rev Bras Hematol Hemoter. 2016;38(4):346–357.
Rozman C, Montserrat E. Chronic lymphocytic leukemia. N Engl J Med 2010;333:1052.
SA, Rabe KG, Kay NE, et al. Chronic lymphocytic leukemia in young (≤ 55 years) patients: a comprehensive analysis of prognostic factors and outcomes. Haematologica. 2014;99(1):140–147.
Saha MN, Qiu L, Chang H. Targeting p53 by small molecules in hematological malignancies. Journal of hematology & oncology. 2013 Mar 27;6(1):23.
Salawu L, Bolarinwa RA, Durosinmi MA. Chronic lymphocytic leukaemia: a-twenty-years experience and problems in Ile-Ife, South-Western Nigeria. Afr Health Sci. 2010;10(2):187–192.
Sall A, Touré AO, Sall FB, et al. Characteristics of chronic lymphocytic leukemia in Senegal. BMC Hematol. 2016;16:10.
Sampath, C. LIU, K. Vasan et al., Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemia, Blood, vol.119, no. 5, pp. 1162-1172, 2012.
Schrock E, du Manoir S, Veldman T et al. Multicolor spectral karyotyping of human chromosomes .Science 1996; 273: 494–497.
Shanafelt TD, Rabe KG, Kay NE, et al. Age at diagnosis and the utility of prognostic testing in patients with chronic lymphocytic leukemia. Cancer. 2010;116(20):4777–4787.
Shanafelt TD, Rabe KG, Kay NE, et al. Age at diagnosis and the utility of prognostic testing in patients with chronic lymphocytic leukemia. Cancer. 2010;116(20):4777–4787.
Sovani V, Harvey C, Haynes AP, McMillan AK, Clark DM, O'connor SR. Bone marrow trephine biopsy involvement by CLL: review of histopathological features correlation with diagnostic biopsy, aspirate and peripheral blood findings. Journal of clinical pathology. 2014 May 1; 67(5):389-95.
Speicher MR, Ballard SG, Ward DC. Karyotyping human chromosomes by combinatorial multi -fluorFISH .Nat Genet 1996; 12: 368–375.
Steven H. Swerdlow, Elias Campo, Stefano A. Pileri, Nancy Lee Harris, Harald Stein, Reiner Siebert, RanjanaAdvani, Michele Ghielmini, Gilles A. Salles, Andrew D. Zelenetz, and Elaine S. Jaffe. Chronic lymphocytic leukemia/small lymphocytic lymphoma.WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues.Blood. 2016 MAY 19; 127(20):2375-2376.
Strati P, Shanafelt TD. Monoclonal B-cell lymphocytosis and early-stage chronic lymphocytic leukemia: diagnosis, natural history, and risk stratification. Blood. 2015 Jul 23; 126(4):454-62.
Tandra P, Krishnamurthy J, Bhatt VR, Newman K, Armitage JO, Akhtari M. Autoimmune cytopenias in chronic lymphocytic leukemia, facts and myths. Mediterranean journal of hematology and infectious diseases. 2013;5(1).
Tandra, Pavankumar et al. “Autoimmune Cytopenias in Chronic Lymphocytic Leukemia, Facts and Myths.” Mediterranean Journal of Hematology and Infectious Diseases 5.1 (2013) PMC.Web. 21 Sept. 2017.
teRaa GD, Kater AP. TP53 dysfunction in CLL: Implications for prognosis and treatment. Best Practice & Research Clinical Haematology. 2016 Mar 31; 29(1):90-9.
Trask BJ. Fluorescence in situ hybridization: applications in cytogenetics and gene mapping .Trends Genet 1991; 7: 149–154.
U. Klein, M. Lia, M. Crespo et al., The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion lead to chronic lymphocytic leukemia, cancer cell, vol. 17, no. 1, pp.28-40, 2010.
Varghese AM, Rawstron AC, Owen RG, Hillmen P. Immunophenotyping of CLL. InNeoplastic Diseases of the Blood 2013 p.71-89.
Vucicevic K, Jakovljevic V, Colovic N, Tosic N, Kostic T, Glumac I, Pavlovic S, Karan-Djurasevic T, Colovic M. Association of Bax Expression and Bcl2/Bax Ratio with Clinical and Molecular Prognostic Markers in Chronic Lymphocytic Leukemia. Journal of Medical Biochemistry. 2016 Apr 1;35(2):150-7.
Wendtner CM, Dreger P, Gregor M, Greil R, Knauf W, Schetelig J, Steurer M, Stilgenbauer S. Chronic lymphocytic leukemia. Onkopedia guidelines 2012.
What are the key statistics for chronic lymphocytic leukemia?.American cancer society. Last Medical Review: 01/06/2017.Last Revised: 02/07/2017. Available at: https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/key-statistics.html.
Zenz T, DӦhner H, Stilgenbauer S. Differential Diagnosis, Staging, and prognostic Factors.In: O’Brien S, Gribben JG chronic lymohocytic leukemia. USA, Informa Healthcare.2008; 7: 103-120.
Zenz T, DӦhner H, Stilgenbauer S. Staging, and Prognostic Factors. In: O’Brien S, Gribben JG chronic lymohocytic leukemia. USA, Informa Healthcare, Inc. 2008; 7: 103-120.
Zenz T, FrӦhling S, Mertens D. Moving from prognostic to predictive factors in chronic lymphocytic leukaemia (CLL). Best Practice & Research Clinical Haematology 2010; 23:71–84.
Zenz T, Mertens D, Küppers R. From Pathogenesis to Treatment of Chronic Lymphocytic Leukaemia. Nat Rev Cancer 2010; 10(1): 37-50.
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